Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholestero...Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.展开更多
Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affectin...Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affecting 50%of the worldwide population,with more than 15 million root canals performed annually in the United States.Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago,such as calcium hydroxide,zinc oxide–eugenol,or even formalin products.Here,we present,for the first time,a nanotherapeutics based on using synthetic highdensity lipoprotein(sHDL)as an innovative and safe strategy to manage dental bone inflammation.sHDL application in concentrations ranging from 25μg to 100μg/mL decreases nuclear factor Kappa B(NF-κB)activation promoted by an inflammatory stimulus(lipopolysaccharide,LPS).Moreover,sHDL at 500μg/mL concentration markedly decreases in vitro osteoclastogenesis(P<0.001),and inhibits IL-1α(P=0.027),TNF-α(P=0.004),and IL-6(P<0.001)production in an inflammatory state.Notably,sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation,mainly by downregulating at least 3-fold the pro-inflammatory genes,such as Il1b,Il1a,Il6,Ptgs2,and Tnf.In vivo,the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to(1.3±0.05)mm^(3) and attenuated the inflammatory reaction after treatment to(1090±184)cells compared to non-treated animals that had(2.9±0.6)mm^(3)(P=0.0123)and(2443±931)cells(P=0.004),thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.展开更多
Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit...Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.展开更多
Objective Inflammation is involved in the development and progression of nonalcoholic fatty liver disease(NAFLD).The monocyte to high-density lipoprotein cholesterol ratio(MHR)has emerged as a marker for various infla...Objective Inflammation is involved in the development and progression of nonalcoholic fatty liver disease(NAFLD).The monocyte to high-density lipoprotein cholesterol ratio(MHR)has emerged as a marker for various inflammation-related diseases.The aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood obesity.Methods Based on hepatic ultrasound,a total of 504 children with obesity(357 with NAFLD and 147 without NAFLD)were included in the study.The correlation between the MHR and NAFLD risk factors was assessed by Pearson’s and Spearman’s analyses.Multivariate stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of NAFLD.Results The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD[0.52(0.44-0.67)versus 0.44(0.34-0.57),P<0.001].Multivariate stepwise logistic regression analysis demonstrated that the MHR[odds ratio(OR):1.033,95%confidence interval(CI):1.015-1.051;P<0.001]was an independent predictor of NAFLD in childhood obesity patients,as were age(OR:1.205,95%CI:1.059-1.371;P=0.005],waist circumference[OR:1.037,95%CI:1.008-1.067;P=0.012],and alanine transaminase[OR:1.067,95%CI:1.045-1.089;P<0.001].Additionally,MHR quartiles showed a significant positive association with the incidence of NAFLD after adjusting for potential confounding factors.Conclusion The present study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity.展开更多
BACKGROUND Lipoprotein(a)[Lp(a)]is a causal risk factor for atherosclerotic cardiovascular diseases;however,its role in acute coronary syndrome(ACS)remains unclear.AIM To investigate the hypothesis that the Lp(a)level...BACKGROUND Lipoprotein(a)[Lp(a)]is a causal risk factor for atherosclerotic cardiovascular diseases;however,its role in acute coronary syndrome(ACS)remains unclear.AIM To investigate the hypothesis that the Lp(a)levels are altered by various conditions during the acute phase of ACS,resulting in subsequent cardiovascular events.METHODS From September 2009 to May 2016,377 patients with ACS who underwent emergent coronary angiography,and 249 who completed≥1000 d of follow-up were enrolled.Lp(a)levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention(PCI)to 48 h after PCI.The primary endpoint was the occurrence of major adverse cardiac events(MACE;cardiac death,other vascular death,ACS,and non-cardiac vascular events).RESULTS The mean circulating Lp(a)level decreased significantly from pre-PCI(0 h)to 12 h after(19.0 mg/dL to 17.8 mg/dL,P<0.001),and then increased significantly up to 48 h after(19.3 mg/dL,P<0.001).The changes from 0 to 12 h[Lp(a)Δ0-12]significantly correlated with the basal levels of creatinine[Spearman’s rank correlation coefficient(SRCC):-0.181,P<0.01]and Lp(a)(SRCC:-0.306,P<0.05).Among the tertiles classified according to Lp(a)Δ0-12,MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups(66.2%vs 53.6%,P=0.034).A multivariate analysis revealed that Lp(a)Δ0-12[hazard ratio(HR):0.96,95%confidence interval(95%CI):0.92-0.99]and basal creatinine(HR:1.13,95%CI:1.05-1.22)were independent determinants of subsequent MACE.CONCLUSION Circulating Lp(a)levels in patients with ACS decreased significantly after emergent PCI,and a greater decrease was independently associated with a worse prognosis.展开更多
AIM:To evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio(MHR)and the disease activity of thyroid-associated ophthalmopathy(TAO).METHODS:A total of 87 patients were classified int...AIM:To evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio(MHR)and the disease activity of thyroid-associated ophthalmopathy(TAO).METHODS:A total of 87 patients were classified into two groups based on clinical activity score(CAS)scoring criteria:high CAS group(n=62,the CAS score was≥3);low CAS group(n=25,the CAS score was<3).In addition,a group of healthy people(n=114)were included to compared the MHR.Proptosis,MHR,average signal intensity ratio(SIR),average lacrimal gland(LG)-SIR,average extraocular muscles(EOM)area from 87 patients with TAO were calculated in magnetic resonance imaging(MRI),and compared between these two groups.Correlation testing was utilized to evaluate the association of parameters among the clinical variables.RESULTS:Patients in high CAS group had a higher proptosis(P=0.041)and MHR(P=0.048).Compared to the healthy group,the MHR in the TAO group was higher(P=0.001).Correlation testing declared that CAS score was strongly associated with proptosis and average SIR,and MHR was positively associated with CAS score,average SIR,and average LG-SIR.The area under the receiver operating characteristic curve(AUC)of MHR was 0.6755.CONCLUSION:MHR,a novel inflammatory biomarker,has a significant association with CAS score and MRI imaging(average SIR and LG-SIR)and it can be a new promising predictor during the active phase of TAO.展开更多
BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has...BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population,particularly concerning non-high-density lipoprotein cholesterol(non-HDL-C).AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.METHODS In this cross-sectional study,thyroid hormone sensitivity indices,the thyroid feedback quantile-based index(TFQI),the thyroid-stimulating hormone index(TSHI),the thyrotrophic T4 resistance index(TT4RI),and the free triiodothyronine(FT3)/free thyroxine(FT4)ratio were calculated.Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels.Random forest variable importance and Shapley Additive Explanations(SHAP)summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.RESULTS Among the 994 participants,389(39.13%)had high non-HDL-C levels.Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI(OR:1.584;95%CI:1.088-2.304;P=0.016),TSHI(OR:1.238;95%CI:1.034-1.482;P=0.02),and TT4RI(OR:1.075;95%CI:1.006-1.149;P=0.032)but was not significantly correlated with the FT3/FT4 ratio.The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex.An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men(OR:1.331;95%CI:1.003-1.766;P=0.048)but elevated TFQI levels in women(OR:2.337;95%CI:1.4-3.901;P=0.001).Among the analyzed variables,the average SHAP values were highest for TSHI,followed by TT4RI.CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.展开更多
Background:Helicobacter pylori(HP)is associated with several gastrointestinal diseases,including peptic ulcer diseases and gastric cancer,and non-gastrointestinal diseases such as hypertension and Alzheimer's dise...Background:Helicobacter pylori(HP)is associated with several gastrointestinal diseases,including peptic ulcer diseases and gastric cancer,and non-gastrointestinal diseases such as hypertension and Alzheimer's disease.However,the relationship between HP and lipid metabolism and atherosclerosis remains unclear.This study aims to investigate the association between H.pylori infection and high-density lipoprotein cholesterol levels and pulse wave conduction velocity.Methods:This is a report of a cross-sectional study that collected data from 2,827 participants.The data collected included results of life questionnaires,laboratory tests,13C-urea breath test(13C-UBT),and pulse wave conduction velocity test.Based on the results of the 13C-UBT test,the subjects were divided into two groups:the HP-uninfected group(HP−)and the HP-infected group(HP+).The study compared the differences in HDL-C levels and brachial-ankle pulse wave velocity(baPWV)between the two groups.One-way regression analysis was used to identify potential factors affecting HDL-C levels in the study population.Multiple regression equations were presented to analyze whether HP infection was an independent risk factor for abnormal HDL-C metabolism in the population.Results:Univariate analysis demonstrated that high-density lipoprotein cholesterol(HDL-C)levels were significantly lower in the HP+group compared to the HP−group,with a mean difference ofβ=−18.1 mg/dl(95%CI:−19.3 to−17.0,P<0.001).After adjusting for all variables,the HDL-C levels remained lower in the HP+group compared to the HP-group,with a mean difference ofβ=−17.4 mg/dl(95%CI:−18.2 to−16.7,P<0.001).These findings suggest that H.pylori infection is independently associated with abnormal HDL-C metabolism.Additionally,brachial-ankle pulse wave velocity(baPWV)was higher in the HP+group than in the HP−group on both sides.On the right side,the baPWV was 1,713.4±231.4 cm/s in the HP+group compared to 1,542.8±237.5 cm/s in the HP−group(t=−18.30,P<0.001).On the left side,the baPWV was 1,743.7±238.8 cm/s in the HP+group compared to 1,562.8±256.3 cm/s in the HP−group(t=−18.23,P<0.001).These results indicate a significant association between H.pylori infection and increased arterial stiffness,as measured by baPWV.Conclusion:Helicobacter pylori infection is associated with a decrease in high-density lipoprotein cholesterol levels and an increase in pulse wave conduction velocity.展开更多
Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially whe...Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially when acute cardiac events occur,such as acute coronary syndrome(ACS)or heart failure.Pharmacotherapy and some mechanical circulatory support(MCS)therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention(PCI).LDL-C is an important pathogenic factor in atherosclerosis,and the target of blood lipid control.Recent studies have revealed that lipoprotein(a)[Lp(a)],which is formed when a covalent bond between apolipoprotein(a)and apolipoprotein B-100 is made,produces an LDL-like particle.This particle is an independent risk factor for the development of atherosclerosis,and is closely correlated to stent thrombosis and restenosis.Furthermore,this requires active intervention.PCSK9 inhibitors have been used in lipid-lowering treatment,and preventing atherosclerosis.The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS,and the association between the change in Lp(a)and survival after 2 years of follow-up.Methods The present real-world,prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020,and these patients were followed up for 2 years.These patients were divided into two groups:PCSK9 group(n=161)given the combined PCSK9 inhibitor(140 mg of evolocumab every 2 weeks)and statins-based therapy,and SOC group(n=160)treated with statin-based lipid-lowering therapy alone.Then,the change in lipid index was measured,and the cardiovascular(CV)event recurrence rate was evaluated after one month and 2 years.Afterwards,the contribution of serum lipid parameters,especially the Lp(a)alteration,in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed.Results The LDL-C level was significantly reduced in both groups:52.3%in the PCSK9 group and 32.3%(P<0.001)in the SOC group.It is noteworthy that the Lp(a)level decreased by 13.2%in the PCSK9 group,but increased by 30.3%in the SOC group(P<0.001).Furthermore,the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period.In the PCSK9 group,the Lp(a)reduction was associated with the baseline Lp(a)levels of the patients(r2=−0.315,P<0.001).Moreover,the decrease in Lp(a)contributed to the decline in CV events in patients who received ACS CHIPs-PCI,and the decrease in Lp(a)level was independent of the LDL-C level reduction.Conclusion The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a)levels in ACS CHIPs-PCI.However,further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.展开更多
基金supported by the National Key R&D Program of China (2022YFE0196200)the National Natural Science Foundation of China–Deutsche Forschungsgemeinschaft of Germany (31761133021)+3 种基金the National Natural Science Foundation of China (31970469 and 31701794)the earmarked fund for Modern Agro-industry Technology Research System, China (2023CYJSTX01-20)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi, China (2017104)the Fund for Shanxi “1331 Project”, China
文摘Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.
基金the National Institutes of Health(NIH–National Institute of Dental and Craniofacial Research,grant R01DE031476)。
文摘Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affecting 50%of the worldwide population,with more than 15 million root canals performed annually in the United States.Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago,such as calcium hydroxide,zinc oxide–eugenol,or even formalin products.Here,we present,for the first time,a nanotherapeutics based on using synthetic highdensity lipoprotein(sHDL)as an innovative and safe strategy to manage dental bone inflammation.sHDL application in concentrations ranging from 25μg to 100μg/mL decreases nuclear factor Kappa B(NF-κB)activation promoted by an inflammatory stimulus(lipopolysaccharide,LPS).Moreover,sHDL at 500μg/mL concentration markedly decreases in vitro osteoclastogenesis(P<0.001),and inhibits IL-1α(P=0.027),TNF-α(P=0.004),and IL-6(P<0.001)production in an inflammatory state.Notably,sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation,mainly by downregulating at least 3-fold the pro-inflammatory genes,such as Il1b,Il1a,Il6,Ptgs2,and Tnf.In vivo,the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to(1.3±0.05)mm^(3) and attenuated the inflammatory reaction after treatment to(1090±184)cells compared to non-treated animals that had(2.9±0.6)mm^(3)(P=0.0123)and(2443±931)cells(P=0.004),thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.
基金supported by the National Natural Science Foundation of China,No.82201460(to YH)Nanjing Medical University Science and Technology Development Fund,No.NMUB20210202(to YH).
文摘Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.
基金supported by the Natural Science Foundation of Zhejiang Province(No.LY22H050001)the Key Project of Provincial Ministry Construction,Health Science and Technology Project Plan of Zhejiang Province(No.WKJ-ZJ-2128)+2 种基金Key Laboratory of Women’s Reproductive Health Research of Zhejiang Province(No.ZDFY2020-RH-0006)the National Natural Science Foundation of China(No.U20A20351)Key Research and Development Plan of Zhejiang Province(No.2021C03079).
文摘Objective Inflammation is involved in the development and progression of nonalcoholic fatty liver disease(NAFLD).The monocyte to high-density lipoprotein cholesterol ratio(MHR)has emerged as a marker for various inflammation-related diseases.The aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood obesity.Methods Based on hepatic ultrasound,a total of 504 children with obesity(357 with NAFLD and 147 without NAFLD)were included in the study.The correlation between the MHR and NAFLD risk factors was assessed by Pearson’s and Spearman’s analyses.Multivariate stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of NAFLD.Results The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD[0.52(0.44-0.67)versus 0.44(0.34-0.57),P<0.001].Multivariate stepwise logistic regression analysis demonstrated that the MHR[odds ratio(OR):1.033,95%confidence interval(CI):1.015-1.051;P<0.001]was an independent predictor of NAFLD in childhood obesity patients,as were age(OR:1.205,95%CI:1.059-1.371;P=0.005],waist circumference[OR:1.037,95%CI:1.008-1.067;P=0.012],and alanine transaminase[OR:1.067,95%CI:1.045-1.089;P<0.001].Additionally,MHR quartiles showed a significant positive association with the incidence of NAFLD after adjusting for potential confounding factors.Conclusion The present study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity.
基金the Vehicle Racing Commemorative Foundation,No.2013-2015Grant for Collaborative Research from Kanazawa Medical University,No.C2015-4and Grants-in-Aid for Scientific Research(C)from the Japan Society for the Promotion of Science to Dr.Kouji Kajinami,No.18K08051 and No.21K08139.
文摘BACKGROUND Lipoprotein(a)[Lp(a)]is a causal risk factor for atherosclerotic cardiovascular diseases;however,its role in acute coronary syndrome(ACS)remains unclear.AIM To investigate the hypothesis that the Lp(a)levels are altered by various conditions during the acute phase of ACS,resulting in subsequent cardiovascular events.METHODS From September 2009 to May 2016,377 patients with ACS who underwent emergent coronary angiography,and 249 who completed≥1000 d of follow-up were enrolled.Lp(a)levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention(PCI)to 48 h after PCI.The primary endpoint was the occurrence of major adverse cardiac events(MACE;cardiac death,other vascular death,ACS,and non-cardiac vascular events).RESULTS The mean circulating Lp(a)level decreased significantly from pre-PCI(0 h)to 12 h after(19.0 mg/dL to 17.8 mg/dL,P<0.001),and then increased significantly up to 48 h after(19.3 mg/dL,P<0.001).The changes from 0 to 12 h[Lp(a)Δ0-12]significantly correlated with the basal levels of creatinine[Spearman’s rank correlation coefficient(SRCC):-0.181,P<0.01]and Lp(a)(SRCC:-0.306,P<0.05).Among the tertiles classified according to Lp(a)Δ0-12,MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups(66.2%vs 53.6%,P=0.034).A multivariate analysis revealed that Lp(a)Δ0-12[hazard ratio(HR):0.96,95%confidence interval(95%CI):0.92-0.99]and basal creatinine(HR:1.13,95%CI:1.05-1.22)were independent determinants of subsequent MACE.CONCLUSION Circulating Lp(a)levels in patients with ACS decreased significantly after emergent PCI,and a greater decrease was independently associated with a worse prognosis.
基金Supported by the Special Fund for Clinical Research of Nanjing Drum Tower Hospital(No.2023-LCYJPY-37).
文摘AIM:To evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio(MHR)and the disease activity of thyroid-associated ophthalmopathy(TAO).METHODS:A total of 87 patients were classified into two groups based on clinical activity score(CAS)scoring criteria:high CAS group(n=62,the CAS score was≥3);low CAS group(n=25,the CAS score was<3).In addition,a group of healthy people(n=114)were included to compared the MHR.Proptosis,MHR,average signal intensity ratio(SIR),average lacrimal gland(LG)-SIR,average extraocular muscles(EOM)area from 87 patients with TAO were calculated in magnetic resonance imaging(MRI),and compared between these two groups.Correlation testing was utilized to evaluate the association of parameters among the clinical variables.RESULTS:Patients in high CAS group had a higher proptosis(P=0.041)and MHR(P=0.048).Compared to the healthy group,the MHR in the TAO group was higher(P=0.001).Correlation testing declared that CAS score was strongly associated with proptosis and average SIR,and MHR was positively associated with CAS score,average SIR,and average LG-SIR.The area under the receiver operating characteristic curve(AUC)of MHR was 0.6755.CONCLUSION:MHR,a novel inflammatory biomarker,has a significant association with CAS score and MRI imaging(average SIR and LG-SIR)and it can be a new promising predictor during the active phase of TAO.
基金Supported by the Xuanwu Hospital Capital Medical University Science Program for Fostering Young Scholars,No.YC20220113the Pilot Project for Public,No.Beijing Medical Research 2021-8.
文摘BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population,particularly concerning non-high-density lipoprotein cholesterol(non-HDL-C).AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.METHODS In this cross-sectional study,thyroid hormone sensitivity indices,the thyroid feedback quantile-based index(TFQI),the thyroid-stimulating hormone index(TSHI),the thyrotrophic T4 resistance index(TT4RI),and the free triiodothyronine(FT3)/free thyroxine(FT4)ratio were calculated.Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels.Random forest variable importance and Shapley Additive Explanations(SHAP)summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.RESULTS Among the 994 participants,389(39.13%)had high non-HDL-C levels.Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI(OR:1.584;95%CI:1.088-2.304;P=0.016),TSHI(OR:1.238;95%CI:1.034-1.482;P=0.02),and TT4RI(OR:1.075;95%CI:1.006-1.149;P=0.032)but was not significantly correlated with the FT3/FT4 ratio.The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex.An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men(OR:1.331;95%CI:1.003-1.766;P=0.048)but elevated TFQI levels in women(OR:2.337;95%CI:1.4-3.901;P=0.001).Among the analyzed variables,the average SHAP values were highest for TSHI,followed by TT4RI.CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.
基金The Sichuan Medical and Health Care Promotion Institute Research Project(KY2022SJ0100).
文摘Background:Helicobacter pylori(HP)is associated with several gastrointestinal diseases,including peptic ulcer diseases and gastric cancer,and non-gastrointestinal diseases such as hypertension and Alzheimer's disease.However,the relationship between HP and lipid metabolism and atherosclerosis remains unclear.This study aims to investigate the association between H.pylori infection and high-density lipoprotein cholesterol levels and pulse wave conduction velocity.Methods:This is a report of a cross-sectional study that collected data from 2,827 participants.The data collected included results of life questionnaires,laboratory tests,13C-urea breath test(13C-UBT),and pulse wave conduction velocity test.Based on the results of the 13C-UBT test,the subjects were divided into two groups:the HP-uninfected group(HP−)and the HP-infected group(HP+).The study compared the differences in HDL-C levels and brachial-ankle pulse wave velocity(baPWV)between the two groups.One-way regression analysis was used to identify potential factors affecting HDL-C levels in the study population.Multiple regression equations were presented to analyze whether HP infection was an independent risk factor for abnormal HDL-C metabolism in the population.Results:Univariate analysis demonstrated that high-density lipoprotein cholesterol(HDL-C)levels were significantly lower in the HP+group compared to the HP−group,with a mean difference ofβ=−18.1 mg/dl(95%CI:−19.3 to−17.0,P<0.001).After adjusting for all variables,the HDL-C levels remained lower in the HP+group compared to the HP-group,with a mean difference ofβ=−17.4 mg/dl(95%CI:−18.2 to−16.7,P<0.001).These findings suggest that H.pylori infection is independently associated with abnormal HDL-C metabolism.Additionally,brachial-ankle pulse wave velocity(baPWV)was higher in the HP+group than in the HP−group on both sides.On the right side,the baPWV was 1,713.4±231.4 cm/s in the HP+group compared to 1,542.8±237.5 cm/s in the HP−group(t=−18.30,P<0.001).On the left side,the baPWV was 1,743.7±238.8 cm/s in the HP+group compared to 1,562.8±256.3 cm/s in the HP−group(t=−18.23,P<0.001).These results indicate a significant association between H.pylori infection and increased arterial stiffness,as measured by baPWV.Conclusion:Helicobacter pylori infection is associated with a decrease in high-density lipoprotein cholesterol levels and an increase in pulse wave conduction velocity.
基金the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(No.ZNLH-201907)the Hubei Province Health and Family Planning Scientific Research Project(No.WJ2019Q041)the Chinese Academy of Medical Science Innovation Fund for Medical Sciences(No.2021-I2M-1-009).
文摘Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially when acute cardiac events occur,such as acute coronary syndrome(ACS)or heart failure.Pharmacotherapy and some mechanical circulatory support(MCS)therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention(PCI).LDL-C is an important pathogenic factor in atherosclerosis,and the target of blood lipid control.Recent studies have revealed that lipoprotein(a)[Lp(a)],which is formed when a covalent bond between apolipoprotein(a)and apolipoprotein B-100 is made,produces an LDL-like particle.This particle is an independent risk factor for the development of atherosclerosis,and is closely correlated to stent thrombosis and restenosis.Furthermore,this requires active intervention.PCSK9 inhibitors have been used in lipid-lowering treatment,and preventing atherosclerosis.The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS,and the association between the change in Lp(a)and survival after 2 years of follow-up.Methods The present real-world,prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020,and these patients were followed up for 2 years.These patients were divided into two groups:PCSK9 group(n=161)given the combined PCSK9 inhibitor(140 mg of evolocumab every 2 weeks)and statins-based therapy,and SOC group(n=160)treated with statin-based lipid-lowering therapy alone.Then,the change in lipid index was measured,and the cardiovascular(CV)event recurrence rate was evaluated after one month and 2 years.Afterwards,the contribution of serum lipid parameters,especially the Lp(a)alteration,in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed.Results The LDL-C level was significantly reduced in both groups:52.3%in the PCSK9 group and 32.3%(P<0.001)in the SOC group.It is noteworthy that the Lp(a)level decreased by 13.2%in the PCSK9 group,but increased by 30.3%in the SOC group(P<0.001).Furthermore,the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period.In the PCSK9 group,the Lp(a)reduction was associated with the baseline Lp(a)levels of the patients(r2=−0.315,P<0.001).Moreover,the decrease in Lp(a)contributed to the decline in CV events in patients who received ACS CHIPs-PCI,and the decrease in Lp(a)level was independent of the LDL-C level reduction.Conclusion The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a)levels in ACS CHIPs-PCI.However,further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.
